Introduction/Background: Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer type and is associated with a poor prognosis.
Cancer-testis antigens (CTA) are specifically expressed in cancer tissue, but not in healthy normal tissue with the exception of testis. Their tumor-restricted expression and immunogenicity makes them an interesting target for specific cancer immunotherapy.
We have previously shown that CTA of the MAGE-A family and NY-ESO-1 serve as independent prognosticators of poor survival. The addition of immunotherapeutic strategies targeting CTA may specifically improve the survival of this group of patients with an increased risk of death. The IRECT trial focuses on tumor host interactions to CTA and human papilloma virus (HPV) during conventional therapy of HNSCC to determine the most promising strategies for integration of immunotherapy targeting CTA or HPV in combination with immune checkpoint modulating drugs.
Material/Methods: The IRECT trial is a single institution non-interventional, prospective clinical trial. HNSCC patients treated with curative intent by surgery followed by (chemo-)radiation as indicated or by primary chemoradiation are monitored over the course of standard-of-care treatment for HNSCC. Snap-frozen and formalin-fixed paraffin embedded tumor tissue was collected at the time of diagnosis/ surgery. Serum, plasma and peripheral blood mononuclear cells (PBMC) are collected at defined time points before and during treatment and at every follow-up after treatment for the first 12 months. Patients were typed for HLA class I and II. CTA mRNA expression for MAGE-A1, -A3, -A4, -C1, -C2, NY-ESO-1 and PRAME was determined by PCR from baseline tumor tissue.
Results: Patient recruitment started 09/2013 at the University Medical Center Ulm. Patient accrual was scheduled for 18 months. A total of 22 patients have been recruited. Mean follow-up was 11.2 months (range: 1-22 months). The primary sites were oropharynx (12/22), larynx (2/22), hypopharynx (3/22) and oral cavity (5/22). Eighteen patients were treated surgically and four patients received primary chemoradiation. To date, two patients had a recurrence (1 locoregional, 1 distant) and two patients developed a second primary tumor (1 HNSCC, 1 pulmonary adenocarcinoma).
Six of 21 evaluable tumors were positive for HPV DNA and 14/21 for at least one of the tested CTA. Ten of the 14 CTA positive patients expressed >1 antigen. Of the 21 evaluable tumors, expression frequencies were as follows: MAGE-A1: 4, MAGE-A3: 11, MAGE-A4: 8, MAGE-C1: 1, MAGE-C2: 1, NY-ESO-1: 2 and PRAME: 10.
Conclusion: Two thirds of the recruited patients expressed at least one of the seven antigens tested. The analysis of immune responses to CTA and HPV during conventional therapy is crucial for a rational integration of cancer immunotherapy into curative HNSCC treatment. This trial will lay the groundwork for a rational integration of cancer-testis antigen or HPV specific vaccines and immune-modulating drugs into the conventional treatment of HNSCC.
As a next step, CTA expression will be confirmed by immunohistochemistry (IHC). A T cell related cytokine panel including Perforin, GM-CSF, sCD137, IFNγ, sFas, sFasL, Granzyme A, Granzyme B, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, MIP-1α, MIP-1β, TNF-α will be quantified by Luminex from 10 defined time points over the course of treatment and for the first 12 months. DAMP will also be quantified over the course of treatment.
Immune infiltrates in the primary tumor will be quantified by IHC. After screening for antibody responses to a panel of tumor associated antigens (primarily CTA) and HPV by Luminex, quantities of selected antigen-specific T cells will be monitored over the course of treatment and during the first 12 months of follow-up by Elispot and tetramer analysis.
Citation Format: Simon Laban, Marie-Nicole Theodoraki, Daniel Fürst, Joannis Mytilineos, Ramin Lotfi, Djordje Atanackovic, Tim Luetkens, Thomas K. Hoffmann. Immunoprofiling head and neck cancer: Preliminary data of the IRECT trial (Immune response evaluation to curative conventional therapy). [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B142.
- ©2016 American Association for Cancer Research.